The Selective Cytopheretic Device (SCD) is an extracorporeal medical device targeted to treat patients with inflammatory disease indications. As patient blood passes through the SCD, it comes in contact with the hemocompatible fibers inside the SCD. These fibers are capable of immunomodulatory interactions with the patient's over-active white blood cells (activated leukocytes). The SCD has been used in three human clinical studies to date, with positive clinical outcomes for critically ill adult patients with acte kidney injury (AKI) and multiorgan dysfunction (MOD). Long term objective: to develop a process to manufacture fibers with an outer diameter (OD) = 140 m, for use in a second generation SCD (SCD2) with low blood fill volumes to enable the treatment of pediatric patients and critically ill adult patients with blood volume removal re- strictions due to potential hemodynamic instability, as well as treatment in out-patient clinics via peripherally inserted central catheter (PICC) access, which require low blood flow rates. Fibers within the current SCD are made of polysulfone (PSu) and have an OD of 280 m. Current technology in hemodialysis fiber manufacturing is restricted to fabricating fibers with OD of between 280 to 600 m. These fibers are far too large to be used in the SCD2, which would cause the blood priming volumes to be high, and therefore not safe for pediatric patients and critically ill patiens. In order to make the blood fill volumes <50 mL for these patients, the fibers must be made =140 m. A lab at Virginia Tech will be used to manufacture fibers of the required specifications for the SCD2 device, which will enable the rapid development of the fiber making process toward clinical translation for the SCD2 to save severely ill patients' lives. In this project, the way in which the SCD works, called the mechanism of action (MoA) will be explored by specifically looking at how white blood cells (WBC) interact with the fibers in the device (Specific Aim 1) by using fresh cow blood from a local slaughterhouse. Production methodology for =140 m OD fibers will be developed by finding just the right balance of polymers to change the surface of the fibers for the best interaction with WBC, also tested with cow blood (Specific Aim 2). The fibers produced in Aim 2 will be sterilized by different methods in Specific Aim 3, and will be tested with cow blood. These optimized, sterilized fibers would be ready for use in a medical device to test in a preclinical large animal model, to prove efficacy. If they are safe and work well, then the finalized devices could be used in a human clinical trial. Health Related Impact: The data generated from this proposal will advance the development of a critical manufacturing process for fabrica- tion of PSu fibers needed to produce SCD2. It will also provide preclinical data for inclusion of regulatory sub- missions to apply for IDE approval from the FDA to initiate clinical trials for the evaluation of SCD2 therapy in both acute and chronic disease indications, including orphan diseases: anti-neutrophil cytoplasmic antibody (ANCA) vasculitis, dermatomyositis, Guillian-Barre Syndrome (GBS), and pediatric AKI.